Organisms vary in their sensitivity to toxic environmental chemicals, depending on genetic and other factors. Genetic variability implies that the structure of exposed populations of plants and animals will change from one generation to the next, based in part upon degree of sensitivity. Sensitive genotypes will be replaced by resistant types over a period of time. Adaptation to contaminated environments could possibly have associated disadvantages. For instance, the ability to survive with a high body burden of contaminants early in life might be accompanied by organ system dysfunctions later on. We are working on methods to isolate mutations relevant to this question using the yeast Saccharomyces cerevisiae. We are currently looking for mutants characterized by diminished or increased ability to survive a heavy-metal-contaminated environment. We have developed a model with lead acetate that has so far produced one unusually sensitive and several resistant lines. We plan to test the model with other substances and characterize the mutations.